• Title/Summary/Keyword: Apoptosis

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A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

  • Wang, Yuequn;Ye, Xiangli;Zhou, Junmei;Wan, Yongqi;Xie, Huaping;Deng, Yun;Yan, Yan;Li, Yongqing;Fan, Xiongwei;Yuan, Wuzhou;Mo, Xiaoyang;Wu, Xiushan
    • BMB Reports
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    • v.44 no.1
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    • pp.58-63
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    • 2011
  • Zinc finger (ZNF) proteins play a critical role in cell growth, proliferation, apoptosis, and intracellular signal transduction. In this paper, we cloned and characterized a novel human KRAB-related zinc finger gene, ZNF425, which encodes a protein of 752 amino acids. ZNF425 is strongly expressed in the three month old human embryos and then is almost undetectable in six month old embryos and in adult tissues. An EGFP-ZNF425 fusion protein can be found in both the nucleus and the cytoplasm. ZNF425 appears to act as a transcription repressor. Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. Our results suggest that the ZNF425 gene is a new transcriptional inhibitor that functions in the MAPK signaling pathway.

Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death

  • Jo, Hyo Sang;Yeo, Hyeon Ji;Cha, Hyun Ju;Kim, Sang Jin;Cho, Su Bin;Park, Jung Hwan;Lee, Chi Hern;Yeo, Eun Ji;Choi, Yeon Joo;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.49 no.5
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    • pp.297-302
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    • 2016
  • Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-γ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases.

ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway

  • Wang, Yuequn;Zhou, Junnei;Ye, Xiangli;Wan, Yongqi;Li, Youngqing;Mo, Xiaoyan;Yuan, Wuzhou;Yan, Yan;Luo, Na;Wang, Zequn;Fan, Xiongwei;Deng, Yun;Wu, Xiushan
    • BMB Reports
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    • v.43 no.3
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    • pp.212-218
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    • 2010
  • Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK-293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions.

Transduced HSP27 protein protects neuronal cell death by enhancing FALS-associated SOD1 mutant activity

  • An, Jae-Jin;Lee, Yeom-Pyo;Kim, Dae-Won;Sohn, Eun-Joung;Jeong, Hoon-Jae;Kang, Hye-Won;Shin, Min-Jae;Kim, Mi-Jin;Ahn, Eun-Hee;Jang, Sang-Ho;Kang, Jung-Hoon;Kang, Tae-Cheon;Won, Moo-Ho;Kwon, Oh-Shin;Cho, Sung-Woo;Lee, Kil-Soo;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.42 no.3
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    • pp.136-141
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    • 2009
  • Familial Amyotrophic lateral sclerosis (FALS) is a progressive neurodegenetative disorder induced by mutations of the SOD1 gene. Heat shock protein 27 (HSP27) is well-defined as a stress-inducible protein, however the its role in ALS protection has not yet been established. To investigate the role HSP27 may have in SOD1 mutant-mediated apoptosis, human SOD1 or HSP27 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame fusion protein, which was then transduced into cells. We found the purified PEP-1-HSP27 fusion proteins can be transduced efficiently into neuronal cells and protect against cell death by enhancing mutant SOD1 activity. Moreover, transduced PEP-1-HSP27 efficiently prevents protein aggregation produced by oxidative stress. These results suggest that transduced HSP27 fusion protein may be explored as a potential therapeutic agent for FALS patients.

Development of Organ Culture Medium for Long Term Culture of Human Hair Follicle (인체 두피 모낭의 장기간 배양을 위한 기관 배양 배지의 개발)

  • Yoo, Bo-Young;Yoon, Hee-Hoon;Shin, Yeon-Ho;Seo, Young-Kwon;Lee, Doo-Hoon;Song, Kye-Yong;Hwang, Sung-Joo;Park, Jung-Keug
    • Korean Chemical Engineering Research
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    • v.44 no.1
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    • pp.58-64
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    • 2006
  • We successfully isolated human anagen hair follicles from human scalp skin by microdissection and tried to culture them under various conditions. First we confirmed negative effect of serum on human hair follicle organ culture. As a next step serum-free medium compositions, Philpott medium, IMDM, and DHGM (Dongguk hair growth medium) were tried. Philpott medium is a general medium for hair organ culture based on Williams' E medium and DHGM is a special self-developed medium containing high amino acids and vitamins (B group) composition. As results, hair follicle in Philpott medium and IMDM showed anagen phase morphological structure, but rapid loss of hair elongation, low alkaline phosphatase expression, and very low expression of CK19. It is thought these hair follicles rapidly regressed from apoptosis. However, hair follicles in DHGM showed long term anagen phase morphological structure, continuous hair elongation, high alkaline phosphatase, and CK19 expression. These results demonstrate that high amino acids and vitamins (B group) composition are essential to in vitro long term human hair follicle organ culture and this culture medium will be useful in basic study of hair biology or application study to the development of alopecia treatment drugs.

Analysis of Studies on Ojeok-san for Establishment of Evidence Based Medicine (EBM 기반 구축을 위한 오적산 연구 논문 분석)

  • Lee, Nam-Hun;Ha, Hye-Kyung;Lee, Ho-Young;Jung, Da-Young;Choi, Ji-Yoon;Lee, Jun-Kyoung;Shin, Hyun-Kyoo
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.1-9
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    • 2008
  • Objective : The purpose of this report was to provide the information about activity and safety of Ojeok-san by analyzing domestic/international papers about Ojeok-san. Methods : Domestic/international papers related to Ojeok-san were reviewed and analyzed. These papers were then classified by year, experimental method and subject. Results : The following results were obtained in this study. 1. The studies of Ojeok-san started from 1984 and has continuously increased. The studies were mainly focused on experimental models rather than clinical studies. 2. By subject, papers related to safety were most common with 5 papers among 20 papers. Besides there were papers related to efficacy of analgesic, anti-hyperlipidemic, anti-blood stasis and treatment for uterine myoma. 3. The papers related to safety were mainly focused on the effect of Okeok-san on liver function, renal function or metal concentration of organs such as blood, brain, liver, kidney and bone. Ojeok-san proved to be safe, but more clinical studies regarding the safety are needed hereafter. 4. Papers related to analgesic, anti-pyretic, anti-phlogistic activities of Ojeok-san were in vivo studies, and other papers were about anti-hyperlipidemic activity, apoptosis inducing activity on uterine myeloma cell line and anti blood static activity on hydrocortisone acetate induced blood statis model. 5. Case reports were about anti-lipidemia, analgesic effect for mastalgia/back pain and anxiety disorder due to climacteric changes. Conclusion : Ojeok-san is being used in various ways with analgesic, anti-pyretic, anti-phlogistic, anti-hyperlipidemic, anti-tumor or anti-blood statis activity. However, mechanism study should be conducted at the molecular biology level and more clinical studies on the efficacy of Ojeok-san are needed.

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The Anticancer Effects and Drug Metabolic Enzyme Change by Intraperitoneal Injection of Agrimonia Pilosa Ledeb (선학초 (짚신나물) 복강주사의 항암효과 탐색 및 약물 대사효소의 변화)

  • Choi, Jung-Won;Jang, Bo-Hyung;Lee, Ju-Ah;Ko, Ho-Yeon;Jung, Hee;Jun, Chan-Yong;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Gyu;Choi, You-Kyung
    • The Journal of Korean Medicine
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    • v.30 no.4
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    • pp.129-141
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    • 2009
  • Objective: This study was to investigate the anti-tumor effect, safety, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB (APL) in female C57B/L mouse tumor (in vivo). Method: First, to evaluate the antitumor activity of APL, we divided the mice into four groups: normal, control, APL50 (50mg/kg), and APL100 (100mg/kg). LLC-obtained American Type Culture Collection was used. LLC had been inoculated to induce tumors. To measure the anti-tumor effect of APL, we calibrated tumor size and weight. To analyze the mechanism of anti-tumor in APL, we used western blotting and to observe metabolizing enzyme in APL we used to real-time PCR. Result: APL50 and APL100 significantly inhibited tumor growth from 12 days after medicine injected. APL did not induce caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it decreased 41% and 71% in CYP2D22 and CYP3A11, respectively. Conclusion: These results suggest that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be used carefully with other drugs related with CYP2D22 and CYP3A11.

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Application on Multi-biomarker Assessment in Environmental Health Status Monitoring of Coastal System (해역 건강도 평가를 위한 다매체 바이오마커 적용)

  • Jung, Jee-Hyun;Ryu, Tae-Kwon;Lee, Taek-Kyun
    • Ocean and Polar Research
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    • v.30 no.1
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    • pp.109-117
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    • 2008
  • Application of biomarkers for assessing marine environmental health risk is a relatively new field. According to the National Research Council and the World Health Organization, biomarkers can be divided into three classes: biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility. In order to assess exposure to or effect of the environmental pollutants on marine ecosystem, the following set of biomarkers can be examined: detoxification, oxidative stress, biotransformation products, stress responses, apoptosis, physiological metabolisms, neuromuscular responses, reproductions, steroid hormones, antioxidants, genetic modifications. Since early 1990s, several biomarker research groups have developed health indices of marine organisms to be used for assessing the state of the marine environment. Biomarker indices can be used to interpret data obtained from monitoring biological effects. In this review, we will summarize Health assessment Index, Biomarker Index, Bioeffect Assessment Index and Generalized Linear Model. Measurements of biomarker responses and development of biomarker index in marine organisms from contaminated sites offer great a lot of information, which can be used in environmental monitoring programs, designed for various aspects of ecosystem risk assessment.

Astaxanthin Inhibits $H_2O_2$-Mediated Apoptotic Cell Death in Mouse Neural Progenitor Cells via Modulation of P38 and MEK Signaling Pathways

  • Kim, Jeong-Hwan;Choi, Woo-Bong;Lee, Jong-Hwan;Jeon, Sung-Jong;Choi, Yung-Hyun;Kim, Byung-Woo;Chang, Hyo-Ihl;Nam, Soo-Wan
    • Journal of Microbiology and Biotechnology
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    • v.19 no.11
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    • pp.1355-1363
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    • 2009
  • In the present study, the neuroprotective effects of astaxanthin on $H_2O_2$-mediated apoptotic cell death, using cultured mouse neural progenitor cells (mNPCs), were investigated. To cause apoptotic cell death, mNPCs were pretreated with astaxanthin for 8 h and followed by treatment of 0.3 mM $H_2O_2$. Pretreatment of mNPCs with astaxanthin significantly inhibited $H_2O_2$-mediated apoptosis and induced cell growth in a dose-dependent manner. In Western blot analysis, astaxanthin-pretreated cells showed the activation of p-Akt, p-MEK, p-ERK, and Bcl-2, and the reduction of p-P38, p-SAPK/JNK, Bax, p-GSK3b, cytochrome c, caspase-3, and PARP. Because $H_2O_2$ triggers caspases activation, this study examined whether astaxanthin can inhibit caspases activation in $H_2O_2$-treated mNPCs. After $H_2O_2$ treatment, caspases activities were prominently increased, but astaxanthin pretreatment significantly inhibited $H_2O_2$-mediated caspases activation. Astaxanthin pretreatment also significantly recovered the ATP production ability of $H_2O_2$-treated cells. These findings indicate that astaxanthin inhibits $H_2O_2$-mediated apoptotic features in mNPCs. Inhibition assays with SB203580 ($10\;{\mu}M$, a specific inhibitor of p38) and PD98059 ($10\;{\mu}M$, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit $H_2O_2$-mediated apoptotic death via modulation of p38 and MEK signaling pathways.

Toxic Effects of Ethylene Glycol on Mammalian Embryo Survivability (Ethylene Glycol이 포유류 초기배자의 생존성에 미치는 독성 효과 분석)

  • Kim, Hyun;Yu, Dae Jung;Choe, Changyong;Seong, Hwan-Hoo
    • Reproductive and Developmental Biology
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    • v.39 no.3
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    • pp.77-81
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    • 2015
  • This study was carried out to evaluate the effects of embryonic stage and toxicities of cryoprotectant on the rates of survival and development of the cryopreserved mouse early embryo and finally to establish the cryopreservation method of surplus embryos obtained during assisted reproductive technology. Toxicities of two cryoprotectants, dimethyl sulfoxide (DMSO) and ethylene glycol (EG) were investigated using a murine embryo model. Female F-1 mice were stimulated with gonadotropin, induced ovulation with hCG and mated. Two cell embryos were collected and cultured after exposure to either DMSO or EG. Embryo development was evaluated up to the blastocyst stage. The total cell count of blastocysts that were treated with DMSO ($68.1{\pm}24.1$) at the 2-cell stage was significantly lower than that were treated with EG ($81.2{\pm}27.0$) or the control ($99.0{\pm}18.3$) (p<0.001). On comparison of two cryoprotectant treated groups, the DMSO treated group showed a decreased cell count compared with the EG treated group (p<0.05). Both DMSO ($15.4{\pm}1.5$) and EG ($10.2{\pm}1.4$) treated groups showed higher apoptosis rates of cells in the blastocyst compared with the control ($6.1{\pm}0.9$, p<0.0001). In addition, the DMSO treated group showed more apoptotic cells than the EG treated group (p<0.001). The potential toxicity of cryoprotectants was uncovered by prolonged exposure of murine embryos to either DMSO or EG at room temperature. When comparing two cryoprotective agents, EG appeared to be less toxic than DMSO at least in a murine embryo model.